Translational kidney research

BACKGROUND AND AIMS: Acute kidney injury (AKI) due to renal ischemia-reperfusion injury (RIRI) is associated with high morbidity and mortality, with no renoprotective drug available. Previous research focused on single drug targets, yet this approach has not reached translational success. Given the complexity of this condition, we aimed to identify a disease module and apply a multitarget network pharmacology approach. METHODS: Identification of a disease module with potential drug targets was performed utilizing Disease Module Detection algorithm using NADPH oxidases (NOXs) as seeds...

We investigated the metabolism and disposition of vornorexant, a novel dual orexin receptor antagonist, in rats and dogs, and clarified in vitro metabolite profiles in humans. Furthermore, we investigated the pharmacokinetics of active metabolites in rats and dogs and their CNS distribution in rats to elucidate its contribution to drug efficacy. [14 C]vornorexant was rapidly and mostly absorbed after the oral administration in rats and dogs. The drug-derived radioactivity, including metabolites, was distributed to major organs such as the liver, kidneys in rats, and was almost eliminated within 24 h post-dose in both species...

Diabetic kidney disease (DKD) is becoming the leading cause of chronic kidney disease, especially in the industrialized world. Despite mounting evidence has demonstrated that immunity and inflammation are highly involved in the pathogenesis and progression of DKD, the underlying mechanisms remain incompletely understood. Substantial molecules, signaling pathways, and cell types participate in DKD inflammation, by integrating into a complex regulatory network. Most of the studies have focused on individual components, without presenting their importance in the global or system-based processes, which largely hinders clinical translation...

BACKGROUND AIMS: Few human induced pluripotent stem cell (hiPSC) lines are Good Manufacturing Practice (GMP)-compliant, limiting the clinical use of hiPSC-derived products. Here, we addressed this by establishing and validating an in-house platform to produce GMP-compliant hiPSCs that would be appropriate for producing both allogeneic and autologous hiPSC-derived products. METHODS: Our standard research protocol for hiPSCs production was adapted and translated into a GMP-compliant platform...

BACKGROUND: Renal microcirculation plays a pivotal role in kidney function by maintaining structural and functional integrity, facilitating oxygen and nutrient delivery, and waste removal. However, a thorough bibliometric analysis in this area remains lacking. Therefore, we aim to provide valuable insights through a bibliometric analysis of renal microcirculation literature using the Web of Science database. METHODS: We collected renal microcirculation-related publications from the Web of Science database from January 01, 1990, to December 31, 2022...

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is a heterogeneous tumor that accounts for a large proportion of kidney cancer, It is prone to recurrence and metastasis, and has a high mortality rate. Although mitophagy is important for metastasis and the recurrence of various tumors, its effect on renal clear cell carcinoma is poorly understood. METHODS: Mitophagy-related genes were obtained through the GeneCards database. We normalised the data from different sources by removing the batch effect...

BACKGROUND: Solute carrier family 31 (copper transporter), member 1 ( SLC31A1 ) is a key factor in maintaining intracellular copper concentration and an important factor affecting cancer energy metabolism. Therefore, exploring the potential biological function and value of SLC31A1 could provide a new direction for the targeted therapy of tumors. METHODS: This study assessed gene expression levels, survival, clinicopathology, gene mutations, methylation levels, the tumor mutational burden (TMB), microsatellite instability (MSI), and the immune cell infiltration of SLC31A1 in pan-cancer using the Tumor Immune Estimation Resource 2...

BACKGROUND: Cancer is a common cause of death around the world. Immunotherapy plays a significant role in cancer treatment but still has limitations. The ankyrin-3 ( ANK3 ) gene has been shown to have a variety of biological roles and has also been shown to be closely linked to individual cancers. METHODS: We systematically investigated the role of ANK3 in pan-cancer, particularly in relation to immunity. We collected data from a number of databases, including the The University of ALabama at Birmingham CANcer data analysis Portal (UALCAN), tumor-immune system interactions (TISIDB), cBioPortal, Tumor Immune Estimation Resource (TIMER), Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), BioGRID, and SangerBox databases...

BACKGROUND: Nephron sparing surgery (NSS) had become the main surgical treatment for bilateral nephroblastoma. But it remained a challenge for surgeons to balance the dilemma between complete tumor resection to reduce tumor recurrence and renal parenchyma preservation to reduce end-stage renal disease (ESRD). In this study, we summarized our clinical experience for bilateral Wilms tumors managed in our center and evaluated the influence of different surgical approaches on prognosis. METHODS: The clinical data of patients with bilateral Wilms tumor in our hospital from January 2010 to December 2020 were retrospectively analyzed, and the clinical symptoms, surgical approaches and prognosis of the disease were summarized...

BACKGROUND: The incidence of chronic kidney disease (CKD) and end-stage kidney disease (ESKD) is increasing worldwide. Hemodialysis (HD) is the mainstay of renal replacement therapy for patients with ESKD. Risk factors associated with late arteriovenous fistula (AVF) failure in HD patients are poorly investigated. Therefore, the aim of this study was to identify factors associated with late AVF failure in HD patients. METHODS: Patients with end-stage renal disease (ESRD) who underwent forearm or upper arm AVF angioplasty at Second Affiliated Hospital of Chongqing Medical University between September 2009 and August 2018 were included...

BACKGROUND AND OBJECTIVE: Inflammatory myofibroblastic tumor (IMT) is a rare entity that is described in several organ systems. This comprehensive review aims to identify IMTs occurring at various genitourinary (GU) organ sites and describe patterns of clinical management in adult and pediatric patients. METHODS: A comprehensive search of PubMed and Web of Science was conducted according to the Preferred Reporting Items for Systematic Review and meta-analyses statement...

While direct cell transplantation holds great promise in treating many debilitating diseases, poor cell survival and engraftment following injection have limited effective clinical translation. Though injectable biomaterials offer protection against membrane-damaging extensional flow and supply a supportive 3D environment in vivo that ultimately improves cell retention and therapeutic costs, most are created from synthetic or naturally harvested polymers that are immunogenic and/or chemically ill-defined. This work presents a shear-thinning and self-healing telechelic recombinant protein-based hydrogel designed around XTEN - a well-expressible, non-immunogenic, and intrinsically disordered polypeptide previously evolved as a genetically encoded alternative to PEGylation to "eXTENd" the in vivo half-life of fused protein therapeutics...

Acute kidney injury (AKI) is a common complication after surgery and the more complex the surgery, the greater the risk. During surgery, patients are exposed to a combination of factors all of which are associated with the development of AKI. These include hypotension and hypovolaemia, sepsis, systemic inflammation, the use of nephrotoxic agents, tissue injury, the infusion of blood or blood products, ischaemia, oxidative stress and reperfusion injury. Given the risks of AKI, it would seem logical to conclude that early identification of patients at risk of AKI would translate into benefit...

Colistin is known to cause nephrotoxicity due to its extensive reabsorption and accumulation in renal tubules. In vitro studies have identified the functional role of colistin transporters such as OCTN2, PEPT2, megalin, and P-glycoprotein. However, the role of these transporter gene variants in colistin-induced nephrotoxicity has not been studied. Utilizing targeted next-generation sequencing, we screened for genetic polymorphisms covering the colistin transporters (SLC15A1, SLC15A2, SLC22A5, LRP2, and ABCB1) in 42 critically ill patients who received colistimethate sodium...

Aflatoxins are harmful natural contaminants found in foods and are known to be hepatotoxic. However, recent studies have linked chronic consumption of aflatoxins to nephrotoxicity in both animals and humans. Here, we conducted a systematic review of active compounds, crude extracts, herbal formulations, and probiotics against aflatoxin-induced renal dysfunction, highlighting their mechanisms of action in both in vitro and in vivo studies. The natural products and dietary supplements discussed in this study alleviated aflatoxin-induced renal oxidative stress, inflammation, tissue damage, and markers of renal function, mostly in animal models...

PURPOSE: Androgen receptors are expressed in the pelvic floor and lower urinary tract. However, the association between serum testosterone and overactive bladder (OAB) in women remains unclear. This study aimed to investigate their association in a nationally representative population. METHODS: In this cross-sectional study, we collected data on female participants older than 20 years with serum total testosterone measurements and OAB questionnaires from the 2011-2016 National Health and Nutrition Examination Survey (NHANES)...

Plasma 4β-hydroxycholesterol (OHC) has drawn attention as an endogenous substrate indicating CYP3A activity. Plasma 4β-OHC is produced by hydroxylation by CYP3A4 and CYP3A5 and by cholesterol autoxidation. Plasma 4α-OHC is produced by cholesterol autoxidation and not affected by CYP3A activity. This study aimed to evaluate the usefulness of plasma 4β-OHC concentration minus plasma 4α-OHC concentration (4β-OHC-4α-OHC) compared with plasma 4β-OHC concentration and 4β-OHC/total cholesterol (TC) ratio in cross-sectional evaluation of CYP3A activity...

BACKGROUND: Bone morphogenetic protein 1 (BMP1) is a metalloprotease that plays a role in activating both transforming growth factor-β (TGF-β) and BMP signaling pathways. TGF-β has been identified as a factor initiating and facilitating cancer development. Consequently, we propose the hypothesis that dysregulation of BMP1 could potentially contribute to the onset and advancement of human cancers. METHODS: In this research, we aimed to analyze BMP1 expression level and the associated clinical outcomes across various cancers using online cancer OMICS databases, advanced Bioinformatics tools, and molecular analyses...

BACKGROUND: Unliteral nephrectomy (UNX) results in the reduction of kidney mass. The remaining kidney undergoes compensatory renal growth via hypertrophy of the glomeruli and renal tubules to maintain a normal glomerular filtration rate (GFR). These compensatory mechanisms result in increased capillary pressure and glomerular hyperfiltration to increase single nephron GFR. Over time, hyperfiltration may lead to kidney scarring and the development of hypertension. OBJECTIVES: The first objective of this study was to test the hypothesis that a 50% reduction in functioning nephrons in juvenile mice leads to increased blood pressure over a 24-hour phase...

BACKGROUND: Human cell division cycle-associated protein 8 (CDCA8), a critical regulator of mitosis, has been identified as a prospective prognostic biomarker in several cancer types, including breast, colon, and lung cancers. This study analyzed the diagnostic/prognostic potential and clinical implications of CDCA8 across diverse cancers. METHODS: Bioinformatics and molecular experiments. RESULTS: Analyzing TCGA data via TIMER2 and GEPIA2 databases revealed significant up-regulation of CDCA8 in 23 cancer types compared to normal tissues...